Hyman Research Publications
Featured Publications
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2023. Shifting the trajectory of therapeutic development for neurological and psychiatric disorders. Science translational medicine. 15(720):eadg4775. Pubmed: 38190501 DOI:10.1126/scitranslmed.adg4775 Krainc D, Martin WJ, Casey B, Jensen FE, Tishkoff S, Potter WZ, Hyman SE. 2023. Shifting the trajectory of therapeutic development for neurological and psychiatric disorders. Science translational medicine. 15(720):eadg4775. Pubmed: 38190501 DOI:10.1126/scitranslmed.adg4775 Clinical trials for central nervous system disorders often enroll patients with unrecognized heterogeneous diseases, leading to costly trials that have high failure rates. Here, we discuss the potential of emerging technologies and datasets to elucidate disease mechanisms and identify biomarkers to improve patient stratification and monitoring of disease progression in clinical trials for neuropsychiatric disorders. Greater efforts must be centered on rigorously standardizing data collection and sharing of methods, datasets, and analytical tools across sectors. To address health care disparities in clinical trials, diversity of genetic ancestries and environmental exposures of research participants and associated biological samples must be prioritized. -
Lähteenvuo M, Ahola-Olli A, Suokas K, Holm M, Misiewicz Z, Jukuri T, Männynsalo T, Wegelius A, Haaki W, Kajanne R, Kyttälä A, Tuulio-Henriksson A, Lahdensuo K, Häkkinen K, Hietala J, Paunio T, Niemi-Pynttäri J, Kieseppä T, Veijola J, Lönnqvist J, Isometsä E, Kampman O, Tiihonen J, Hyman S, Neale B, Daly M, Suvisaari J, Palotie A. 2023. Cohort profile: SUPER-Finland - the Finnish study for hereditary mechanisms of psychotic disorders. BMJ open. 13(4):e070710. Pubmed: 37045567 DOI:10.1136/bmjopen-2022-070710 Lähteenvuo M, Ahola-Olli A, Suokas K, Holm M, Misiewicz Z, Jukuri T, Männynsalo T, Wegelius A, Haaki W, Kajanne R, Kyttälä A, Tuulio-Henriksson A, Lahdensuo K, Häkkinen K, Hietala J, Paunio T, Niemi-Pynttäri J, Kieseppä T, Veijola J, Lönnqvist J, Isometsä E, Kampman O, Tiihonen J, Hyman S, Neale B, Daly M, Suvisaari J, Palotie A. 2023. Cohort profile: SUPER-Finland - the Finnish study for hereditary mechanisms of psychotic disorders. BMJ open. 13(4):e070710. Pubmed: 37045567 DOI:10.1136/bmjopen-2022-070710 Array© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. -
Nehme R, Pietiläinen O, Artomov M, Tegtmeyer M, Valakh V, Lehtonen L, Bell C, Singh T, Trehan A, Sherwood J, Manning D, Peirent E, Malik R, Guss EJ, Hawes D, Beccard A, Bara AM, Hazelbaker DZ, Zuccaro E, Genovese G, Loboda AA, Neumann A, Lilliehook C, Kuismin O, Hamalainen E, Kurki M, Hultman CM, Kähler AK, Paulo JA, Ganna A, Madison J, Cohen B, McPhie D, Adolfsson R, Perlis R, Dolmetsch R, Farhi S, McCarroll S, Hyman S, Neale B, Barrett LE, Harper W, Palotie A, Daly M, Eggan K. 2022. The 22q11.2 region regulates presynaptic gene-products linked to schizophrenia. Nature communications. 13(1):3690. Pubmed: 35760976 DOI:10.1038/s41467-022-31436-8 Nehme R, Pietiläinen O, Artomov M, Tegtmeyer M, Valakh V, Lehtonen L, Bell C, Singh T, Trehan A, Sherwood J, Manning D, Peirent E, Malik R, Guss EJ, Hawes D, Beccard A, Bara AM, Hazelbaker DZ, Zuccaro E, Genovese G, Loboda AA, Neumann A, Lilliehook C, Kuismin O, Hamalainen E, Kurki M, Hultman CM, Kähler AK, Paulo JA, Ganna A, Madison J, Cohen B, McPhie D, Adolfsson R, Perlis R, Dolmetsch R, Farhi S, McCarroll S, Hyman S, Neale B, Barrett LE, Harper W, Palotie A, Daly M, Eggan K. 2022. The 22q11.2 region regulates presynaptic gene-products linked to schizophrenia. Nature communications. 13(1):3690. Pubmed: 35760976 DOI:10.1038/s41467-022-31436-8 It is unclear how the 22q11.2 deletion predisposes to psychiatric disease. To study this, we generated induced pluripotent stem cells from deletion carriers and controls and utilized CRISPR/Cas9 to introduce the heterozygous deletion into a control cell line. Here, we show that upon differentiation into neural progenitor cells, the deletion acted in trans to alter the abundance of transcripts associated with risk for neurodevelopmental disorders including autism. In excitatory neurons, altered transcripts encoded presynaptic factors and were associated with genetic risk for schizophrenia, including common and rare variants. To understand how the deletion contributed to these changes, we defined the minimal protein-protein interaction network that best explains gene expression alterations. We found that many genes in 22q11.2 interact in presynaptic, proteasome, and JUN/FOS transcriptional pathways. Our findings suggest that the 22q11.2 deletion impacts genes that may converge with psychiatric risk loci to influence disease manifestation in each deletion carrier.© 2022. The Author(s). -
Hyman, SE. 2021. Psychiatric disorders: Grounded in human biology but not natural kinds. Perspectives in Biology and Medicine. 64(1):6-28. DOI:10.1353/pbm.2021.0002 Hyman, SE. 2021. Psychiatric disorders: Grounded in human biology but not natural kinds. Perspectives in Biology and Medicine. 64(1):6-28. DOI:10.1353/pbm.2021.0002 The third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) and its descriptive psychiatry-based intellectual antecedents imagined psychiatric disorders as discontinuous categories, presumably natural kinds, that would be empirically validated based on future scientific studies. Validation would emerge from a predicted convergence of clinical descriptions (symptom clusters that could be shown to be stable over the lifespan), laboratory results, and family studies. That future science is now arriving, but rather than validating the categorical DSM approach, large-scale genetics along with modern neurobiology and epidemiology have emphatically undercut it. Clinical description, laboratory studies, and family (now genetic) studies do not converge at all on distinct categories. Rather, modern studies are consistent with psychiatric disorders as heterogeneous quantitative deviations from health. The characteristics of these disorders have proven to be discoverable rather than invented and thus are grounded in nature. However, scientific results demonstrate that psychiatric disorders cannot reasonably be understood as discrete categories-and certainly not as natural kinds. -
Turley P, Meyer MN, Wang N, Cesarini D, Hammonds E, Martin AR, Neale BM, Rehm HL, Wilkins-Haug L, Benjamin DJ, Hyman S, Laibson D, Visscher PM. 2021. Problems with Using Polygenic Scores to Select Embryos. The New England journal of medicine. 385(1):78-86. Pubmed: 34192436 DOI:10.1056/NEJMsr2105065 Turley P, Meyer MN, Wang N, Cesarini D, Hammonds E, Martin AR, Neale BM, Rehm HL, Wilkins-Haug L, Benjamin DJ, Hyman S, Laibson D, Visscher PM. 2021. Problems with Using Polygenic Scores to Select Embryos. The New England journal of medicine. 385(1):78-86. Pubmed: 34192436 DOI:10.1056/NEJMsr2105065 Companies have recently begun to sell a new service to patients considering in vitro fertilization: embryo selection based on polygenic scores (ESPS). These scores represent individualized predictions of health and other outcomes derived from genomewide association studies in adults to partially predict these outcomes. This article includes a discussion of many factors that lower the predictive power of polygenic scores in the context of embryo selection and quantifies these effects for a variety of clinical and nonclinical traits. Also discussed are potential unintended consequences of ESPS (including selecting for adverse traits, altering population demographics, exacerbating inequalities in society, and devaluing certain traits). Recommendations for the responsible communication about ESPS by practitioners are provided, and a call for a society-wide conversation about this technology is made. (Funded by the National Institute on Aging and others.).Copyright © 2021 Massachusetts Medical Society.